Rosmarinic Acid Present in Lepechinia floribunda and Lepechinia meyenii as a Potent Inhibitor of the Adenylyl Cyclase gNC1 from Giardia lamblia

ZURITA, ADOLFO; VEGA HISSI, ESTEBAN; CIANCI ROMERO, AGOSTINA; LUJÁN, ADELA MARÍA; SALIDO, SOFÍA; YANEFF, AGUSTÍN; DAVIO, CARLOS; COBO, JUSTO; CARPINELLA, MARÍA CECILIA; ENRIZ, RICARDO DANIEL

Plants

MDPI

Año: 2024 vol. 13

Giardiasis is a parasitosis caused by Giardia lamblia with significant epidemiological andclinical importance due to its high prevalence and pathogenicity. The lack of optimal therapies fortreating this parasite makes the development of new effective chemical entities an urgent need. Inthe search for new inhibitors of the adenylyl cyclase gNC1 obtained from G. lamblia, 14 extractsfrom Argentinian native plants were screened. Lepechinia floribunda and L. meyenii extracts exhibitedthe highest gNC1 inhibitory activity, with IC50 values of 9 and 31 μg/mL, respectively. In silicostudies showed rosmarinic acid, a hydroxycinnamic acid present in both mentioned species, to be apromising anti-gNC1 compound. This result was confirmed experimentally, with rosmarinic acidshowing an IC50 value of 10.1 μM. Theoretical and experimental findings elucidate the molecular-level mechanism of rosmarinic acid, pinpointing the key interactions stabilizing the compound–enzyme complex and the binding site. These results strongly support that rosmarinic acid is a promising scaffold for developing novel compounds with inhibitory activity against gNC1, which could serveas potential therapeutic agents to treat giardiasis.